Heart Rate Variability Predicts Treatment Response in Anxious Depression

Human heart artwork
Human heart artwork
Investigators assessed the utility of pretreatment heart rate variability for treatment outcomes in patients with major depressive disorder.

In cases of anxious depression, pretreatment high-frequency heart rate variability is a significant biomarker for predicting antidepressant response in patients with major depressive disorder, according to study results published in Depression and Anxiety.

The investigators of this large randomized, multicenter study sought to determine whether pretreatment heart rate variability could predict outcomes of antidepressant medications in patients with major depressive disorder and whether pretreatment anxiety moderated the effects of heart rate variability in this population.

The study included 722 patients diagnosed with nonpsychotic major depressive disorder recruited from 17 international sites and managed by 3 treatment arms: escitalopram, sertraline, and extended release venlafaxine. During pretreatment assessment, investigators categorized the patients as having anxious depression (n=309) or nonanxious depression (n=413) and measured each participant’s resting heart rate variability. After 8 weeks, symptom severity was reassessed, and the treating clinician rated the primary study outcomes of symptom response and remission to antidepressants. Patient-reported symptom response and remission were secondary outcomes. Investigators used logistic regression models to examine the power of heart rate variability as a predictor of treatment outcomes, as well as anxious vs nonanxious depression as a moderator of heart rate effects on antidepressants.

The study results indicated that pretreatment heart rate variability was a predictor of antidepressant outcomes and was significantly affected by interactions of anxious vs nonanxious depression. In the group with anxious depression, patients with higher heart rate variability had better outcomes. In the nonanxious depression group, patients with lower heart rate variability generally had better outcomes. However, the effects in this group were not deemed significant. When controlling for variables, the study results were similar and remained significant across treatment arms.

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Limitations to the study included the possibility that patients taking medication at the start of study predicted different effects and that comorbid cardiovascular and respiratory conditions impacted heart rate variability. Neither the participants nor the treating clinicians were blind to their treatment assignment, and the study did not include a control group. Finally, high-frequency heart rate variability utilized relatively short durations (4 minutes) and were not assessed after treatment.

The investigators concluded that measuring heart rate variability could be useful for predicting treatment outcomes in patients with anxious depression. Understanding the modifying effect of anxiety on heart rate variability in patients with depression can further help identify individuals who may benefit from antidepressants vs individuals who may require a different treatment approach.

One author declared potential conflicts of interest. Please see original reference for a full list of authors’ disclosures.


Kircanski K, Williams LM, Gotlib IH. Heart rate variability as a biomarker of anxious depression response to antidepressant medication [published online October 12, 2018]. Depress Anxiety. doi:10.1002/da.22843